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Autocrine regulation of gonadotropin-releasing hormone (GnRH) operates at multiple control levels of GnRH gene expression in GT1-1 neuronal cells

Animal Cells and Systems 1998년 2권 4호 p.483 ~ 488
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Abstract


We previously found that a potent gonadotropin?releasing hormone (GnRH) agonist, buserelin, decreases GnRH promoter activity together with GnRH mRNA level, providing evidence for an autoregulatory mechanism operating at the level of GnRH gene transcription in immortalized GT1?1 neuronal cells. To examine whether agonist?induced decrease in GnRH mRNA level requires the continuous presence of buserelin, we performed a pulse?chase experiment of buserelin treatment. Short?term exposure (15min) of GT1?1 neuronal cells to buserelin (10 μM) was able to decrease GnRH mRNA levels when determined 24 h later. When GT1?1 cells were treated with buserelin (10 uM) for 30min and then incubated for 1, 3, 6, 12, 24, and 48 h after buserelin removal, a significant decrease in GnRH mRNA levels was observed after the 12 h incubation period. These data indicate that inhibitory signaling upon buserelin treatment may occur rapidly, but requires a long time (at least 12 h) to significantly decrease the GnRH mRNA level. To examine the possible involvement of de novo synthesis and/or mRNA stability in buserelin?induced decrease in GnRH gene expression, actinomycin D (5 μg/ml), a potent RNA synthesis blocker, was co?treated with buserelin. Actinomycin D alone failed to alter basal GnRH mRNA level, but blocked the buserelin?induced decrease in GnRH mRNA level at 12 h of post?treatment. These data suggest that buserelin may exert its inhibitory action by altering the stability of GnRH mRNA. Moreover, a polysomal RNA separation by sucrose gradient centrifugation demonstrated that buserelin decreased the translational efficiency of the transcribed GnRH mRNA. Taken together, these results clearly indicate that GnRH agonist buserelin acts as an inhibitory signal at multiple levels such as transcription, mRNA stability, and translation.

키워드

Gonadotropin-releasing hormone; GT1-1 cells; mRNA stability; Translation efficiency

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